PrEP in Scotland - Local data and implementation issues Dr Dan Clutterbuck Consultant in Genitourinary & HIV medicine NHS Lothian

Programme Local data Implementation challenges Some clinical questions Monitoring issues Start, stop and missed doses

Source of content An email to all Sexual Health Clinical Leads The one or two greatest practical challenges you have encountered in providing NHS PrEP locally One or two unanswered PrEP questions (clinical or otherwise) If possible, at the end of August, the number of individuals you've started on PrEP in your board. Prescribing PrEP Updating the i-base UK Guide to PrEP Contributing to the BASHH/BHIVA Guideline

Number of individuals commencing NHS funded PrEP, Scotland by mainland Health Board to 31st August 2017

Number of individuals commencing NHS funded PrEP, Scotland by mainland Health Board to 31st August 2017 A+A 6 Borders 3 D+G 2 Fife 15 FV 18 Grampian 50 GG&C 200 Highland 13 Lanarkshire 10 Lothian 84 (+37 DISCOVER trial) Tayside 13 Scotland 404

Implementation challenges Speed of implementation Capacity building and planning Staff confidence Even among GUM trained staff ‘realising how few members of staff feel even slightly comfortable prescribing PrEP’ Increase in STIs Difficult to quantify as yet

Capacity issues Capacity planning Additional consultant/medical/nursing sessions Appropriate expertise Task shifting (nurses, CSWs) Accommodating reviews and first returns Decisions about reviewing results Increasing STI and partner notification workload

Capacity planning

Clinic implementation Appropriately trained staff vs flexibility Training opportunities and capacity Opportunistic starts (efficiency) vs waiting list (equity) Reviewing results (safety) vs capacity (appointments) 1 month reviews

Eligibility criteria Residency Anxieties about establishing residency ‘Proof of residency’ Equivalent criteria Criteria 4 Guidance from PHE imminent Low(er) risk MSM

Positive effects Attendance of individuals at risk Discussions about risk Increased disclosure of risk Referrals for behaviour change

Monitoring issues Waiting for and checking baseline biochemistry Delayed samples High potassium High phosphate Which tests to do? Bone profiles LFTs Urinalysis, uPCR

Clinical challenges

What are the markers of toxicity? Renal toxicity Monitoring for significant reduction in eGFR Or are we monitoring for tubular dysfunction with normal eGFR? Proteinuria as a marker of reduced eGFR ? Relevance of low phosphate in isolation?

Dosing issues On demand (Event based) vs continuous Starting and stopping Missed doses Indications for PEPSE Defining by gender/position/genital mucosa ‘perhaps lead-in/out times could be defined by tissue/mucosal site and not by risk group’

Dosing – some pointers Differences between absorption and time to steady state for anal, rectal and vaginal tissues and PBMCs Good data on rectal concentrations, less on vaginal and none on male genital (urethra, glans, foreskin) HIV takes 8-24 hours to be established – about 8 hours for the first round of replication. Drug levels at second round of replication is probably critical

Drug levels FTC reaches protective levels faster (30mins, 4 hours for active metabolite), and concentrate more in vaginal tissue, but FTC-DP levels fall rapidly TDF concentrates in rectal tissue and TDF-DP remains detectable for 14 days after a single dose Both drugs concentrate in rectal tissue, TDF concentrates much more in PBMCs

Dosing advice A lead time of seven days is sufficient for all individuals There is considerable evidence that 3 days may be sufficient for anal AND receptive vaginal sex Continue for 48 hours (2 doses) after last exposure for anal sex, insertive penile sex and 7 days for vaginal/frontal sex For on-demand dosing (anal sex only), 24 hours pre exposure is ideal, but 2 hours before is effective and it is still worth taking the double dose AFTER exposure

Missed doses and PEPSE Missed doses ‘How bad does your adherence have to be before we advise PEP’ ‘It would be great if we could have some missed pill rules as they do for COC’

Some missed pill rules for debate PEPSE should hardly ever be indicated for anal sex exposures on PrEP 4 or more doses in the previous week – no PEPSE Double dose prior to sex and 1 dose in the 48 hours after – no PEPSE?

Coding and data Financial anxieties mean prescription data is well recorded Reconciling attendance, NaSH prescribing and pharmacy data STISS coding reinstated for PrEP Guidance issued 4th September Applies retrospectively Clinical training and quality control required

Thanks Lothian PrEP and Discover trial teams Scottish Lead Clinicians and PrEP clinicians Rak and the PrEP SLWG members Simon Collins, Sheena McCormack and the ibase leaflet co-authors Monica Desai, Sheena McCormack and BHIVA guideline co-authors PrEPMAR members

Discussion Sharing of learning Email forum? PrEP seminar at BASHH/BHIVA Annual Conference 2018 Lead Clinicians discussions and SLWG subgroups PrEP meeting?

IPrEx renal monitoring Urine dipstick results Urine dipstick results at follow-up included data from 1589 participants at 5081 visits; routine testing (764 participants and 2748 visits) was performed at five clinical sites. Of 5081 dipsticks, 613 were positive for proteinuria (12%) and 62 (1%) were positive for glucosuria. Of those positive for proteinuria, four were associated with a confirmed creatinine elevation [positive predictive value (PPV) for confirmed creatinine elevation 0.7%]. Of the 62 dipsticks positive for glucosuria, none were associated with a confirmed creatinine elevation (PPV forconfirmed creatinine elevation 0%).